摘要目的 观察叔丁基对苯二酚(tBHQ)对2型糖尿病(DM)大鼠视网膜组织中核因子E2相关因子(Nrf2)、血红素氧合酶1(HO-1)表达的影响.方法 健康雄性Sprague Dawley大鼠60只,随机抽取20只大鼠为正常对照组(NC组),其余40只大鼠为造模组.造模组大鼠腹腔注射30 mg/kg剂量链脲佐菌素诱导2型DM模型.剔除血糖恢复鼠5只,造模组随机分成DM组、tBHQ组,分别为17、18只大鼠.tBHQ组大鼠给予添加1％tBHQ的高脂高糖饲料喂养.tBHQ喂养后4、12周,苏木精-伊红染色观察大鼠视网膜组织结构;免疫组织化学染色法检测大鼠视网膜组织中Nrf2、HO-1蛋白表达;荧光定量聚合酶链反应(PCR)测定大鼠视网膜组织中Nrf2、HO-1mRNA表达.结果 光学显微镜观察,4周时,tBHQ组大鼠视网膜细胞排列较整齐,个别细胞可见轻度水肿;12周时,视网膜组织结构较清晰,部分细胞水肿.免疫组织化学染色结果显示,4、12周时,DM组大鼠视网膜组织中Nrf2(t=3.115、3.781)、HO-1(f=3.485、3.785)蛋白表达较NC组增多,差异均有统计学意义(P＜0.01).tBHQ组大鼠视网膜组织中Nrf2(t=2.473、2.576)、HO-1(t=2.785、2.879)蛋白表达较DM组增多,差异有统计学意义(P＜0.05).DM组组内比较,12周大鼠视网膜中Nrf2蛋白表达较4周时增高,差异有统计学意义(t=0.276,P＜0.05);tBHQ组组内比较,12周大鼠视网膜中Nrf2(t=2.516)、HO-1(t=2.776)蛋白表达较4周时增高,差异有统计学意义(P＜0.05).荧光定量PCR检测结果显示,4、12同时,DM组大鼠视网膜组织中Nrf2(t=4.758、4.285)、HO-1 mRNA(t=5.114、4.514)表达较NC组增多,差异有统计学意义(P＜0.05);tBHQ组大鼠视网膜组织中Nrf2(t=5.133、4.976)、HO 1 mRNA(t=4.758、4.251)表达较DM组增多,差异有统计学意义(P＜0.05).DM组组内比较,12周时视网膜组织中Nrf2 mRNA表达高于4周,差异有统计学意义(t=5.114,P＜0.05);tBHQ组组内比较,12周时视网膜组织中Nrf2、HO-1 mRNA表达高于4周,差异有统计学意义(t=4.292、4.974,P＜0.05).结论 tBHQ干预可以有效诱导2型DM大鼠视网膜组织中Nrf2、HO-1的表达.

abstractsObjective To observe the effect of tert butyl hydroquinone (tBHQ) on type 2 diabetic rats retinal nuclear factor E2 related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1).Methods 60 Sprague Dawley rats were randomly divided into normal control group (NC group, n=20) and model group (n=40).The rats in model group were intraperitoneal injected with streptozotocin (30 mg/kg) to establishing type 2 diabetic mellitus (DM).There were 35 rats successfully established and they were randomly divided into diabetic group (DM group, 17 rats) and tBHQ group (18 rats).The rats in tBHQ group were fed with high fat and sugar diet with 1％ tBHQ.After 4 weeks and 12 weeks of tBHQ intervention, hematoxylin eosin staining of retinal sections, immunohistochemical staining and quantitative polymerase chain reaction (PCR) of Nrf2 and HO-1 were performed.Results In tBHQ control, the retina of rats was normal and individual cells showed slightly edema at 4 weeks;the retinal structure of rats was clear and part of cells showed edema at 12 weeks.At 4 and 12 weeks, the expression of Nrf2 (t=3.115, 3.781) and HO-1 (t=3.485, 3.785) protein in DM group were higher than that in NC group (P＜0.05);the expression of Nrf2 (t=2.473, 2.576) and HO-1 (t=2.785, 2.879) protein in tBHQ group were higher than that in DM group (P＜0.05).In DM group, the expression of Nrf2 protein at 12 weeks was higher than that at 4 weeks (t=0.276, P＜0.05).In tBHQ group, the expression of Nrf2 (t=2.516) and HO-1 (t=2.776) protein at 12 weeks were higher than that at 4 weeks (P＜0.05).4 and 12 weeks, the expression of Nrf2 (t=4.758,4.285) and HO-1 (t=5.114, 4.514) mRNA in DM group were higher than that in NC group (P＜0.05);the expression of Nrf2 (t=5.133, 4.976) and HO-1 (t=4.758, 4.251) mRNA in tBHQ group were higher than that in DM group (P＜0.05).In DM gruop, the expression of Nrf2 protein at 12 weeks was higher than that at 4 weeks (t=5.114, P＜0.05).In tBHQ group, the expression of Nrf2 (t=4.292) and HO-1 (t=4.974) protein at 12 weeks were higher than that at 4 weeks (P ＜ 0.05).Conclusion tBHQ intervention can increased the expression of Nrf2, HO-1 significantly in the retina of type 2 diabetic rats.